大网膜包裹明胶-间充质干细胞复合物对马兜铃酸肾病保护作用的研究  

Protective effect of omentum-encapsulated gelatin-mesenchymal stem cells complex on aristolochic acid nephropathy

作　　者：付章宁 宋成成 耿晓东[2,3] 迟坤 洪权 吴镝[2] Fu Zhangning;Song Chengcheng;Geng Xiaodong;Chi Kun;Hong Quan;Wu Di(Chinese PLA Medical School,Beijing 100853;Department of Nephrology,First Medical Center of Chinese PLA General Hospital,Chinese PLA Institute of Nephrology,State Key Laboratory of Kidney Diseases,National Clinical Research Center for Kidney Diseases,Beijing Key Laboratory of Kidney Diseases,Beijing 100853;Chinese PLA Joint Logistics Support Force Beidaihe Rehabilitation Center,Qinhuangdao 066100,Hebei Province,China)

机构地区：[1]解放军医学院,北京100853 [2]解放军总医院第一医学中心肾脏病医学部、解放军肾脏病研究所、肾脏疾病国家重点实验室、国家慢性肾病临床医学研究中心、肾脏疾病研究北京市重点实验室,北京100853 [3]联勤保障部队北戴河康复疗养中心,秦皇岛066100

出　　处：《中华肾病研究电子杂志》2022年第1期7-14,共8页Chinese Journal of Kidney Disease Investigation（Electronic Edition）

基　　金：国家自然科学基金面上项目(81870491,82070741);解放军总医院“国家杰出青年科学基金”培育专项(2019-JQPY-002)

摘　　要：目的研究大网膜包裹明胶-间充质干细胞(MSCs)复合物对马兜铃酸肾病(AAN)小鼠肾脏的修复和保护作用。方法使用明胶与间充质干细胞共培养构建间充质干细胞-明胶复合物。用CCK-8法评价MSCs与明胶的生物相容性以及MSCs的增殖能力。将体重为20~25 g的健康雄性C57BL/6小鼠24只随机分为4组:正常对照组(Control组)、马兜铃酸肾病模型组(AAN组,腹腔注射马兜铃酸溶液)、大网膜包裹MSCs治疗组(MSCs组)、大网膜包裹MSCs-明胶复合物治疗组(MSCs-Gel组)。利用小动物活体成像系统观察MSCs在小鼠体内的分布和存活情况;检测各组小鼠的血肌酐、尿素氮水平变化,观察肾脏组织学变化及相关纤维化指标如α-SMA、TGF-β和胶原变化情况。结果明胶对MSCs的增殖能力无明显影响。与单纯MSCs组相比,MSC-Gel组的MSCs在小鼠肾脏内存活时间更长,且血肌酐、尿素氮明显降低,肾组织病理改变纤维化程度明显减轻,α-SMA、TGF-β、Col-Ⅰ表达亦显著降低(均P<0.05)。结论大网膜包裹明胶-MSCs复合物对AAN小鼠肾脏具有良好的修复和保护作用。Objective To investigate the repair and protective effects of omentum-encapsulated gelatin-mesenchymal stem cells(MSCs)complex on the kidneys of mice with aristolochic acid nephropathy(AAN).Methods The MSCs-gelatin complex was made by co-culture of gelatin and MSCs.The biocompatibility between MSCs and gelatin as well as the proliferation ability of MSCs were evaluated with the CCK-8.Twenty-four healthy male C57 BL/6 mice weighing 20-25 g were randomly divided into 4 groups:control group(normal mice),AAN model group(intraperitoneal injection of aristolochic acid solution),MSCs group(greater omentum-encapsulated MSCs),and MSCs-Gel group(greater omentum-encapsulated MSCs plus gelatin complex).An in vivo fluorescence imaging system was used to observe the distribution and survival of MSCs in mice.The levels of serum creatinine and blood urea nitrogen of the mice were measured.The renal histological changes and fibrosis indicators such asα-SMA,TGF-β,and collagen were also evaluated.Results The gelatin had no significant influence on the proliferation ability of MSCs.Compared with the MSCs group,the MSC-Gel group showed significantly longer survival of the MSCs in the mice kidneys,lower levels of serum creatinine and blood urea nitrogen,less expression ofα-SMA,TGF-β,and collagenⅠ,and lower level of renal fibrosis(P<0.05).Conclusion The omentum-encapsulated gelatin-MSCs complex had good repair and protective effects on the kidneys of AAN mice.

关 键 词：大网膜 明胶 间充质干细胞 马兜铃酸肾病 

分 类 号：R692[医药卫生—泌尿科学]